Dialkyltin salts of substituted pyridine-1-oxides

ABSTRACT

CERTAIN DIALKYLTIN SALT OF 2-MERCAPTOPYRIDINE-1-OXIDE AND 2-HYDROXYPYRIDINE-1-OXIDE ARE PREPARED BY REACTING THE RESPECTIVE OXIDES WITH A DIALKYLTIN SALT OF A LOW MOLECULAR WEIGHT ORGANIC OR INORGANIC ACID. THE RESULTING SALTS ARE HIGHLY EFFECTIVE BACTERICIDES AND FUNGICIDES WHICH HAVE ESPECIALLY LOW TOXICITY TO HIGHER ANIMALS.

United States Patent 3,787,417 DIALKYLTIN SALTS 0F SUBSTITUTED PYRIDlNE-l-OXIDES Charles W. Kaufman, Hamdeu, Conn., assignor to Olin Corporation No Drawing. Application July 18, 1969, Ser. No. 843,218,

now Patent No. 3,705,943, which is a continuation-1npart of abandoned application Ser. No. 596,801, Nov. 25, 1966. Divided and this application June 28, 1972, Ser. No. 266,948

Int. Cl. C07d 29/36 US. Cl. 260-270 R 8 Claims ABSTRACT OF THE DISCLOSURE Certain dialkyltin salts of Z-mercaptopyridine-l-oxide and 2-hydroxypyridine-1-oxide are prepared by reacting the respective oxides with a dialkyltin salt of a low molecular weight organic or inorganic acid. The resulting salts are highly effective bactericides and fungicides which have especially low toxicity to higher animals.

formula Sn0h RI! L wherein R and R" are independently selected from the group consisting of alkyl of from 4 to 8 carbon atoms and Ch is a chalcogen selected from the group consisting of sulfur and oxygen.

The compound herein referred to as Z-mercaptopyridine-l-oxide, although generally represented as:

is believed to be a mixture of two tautomeric isomers as follows:

N//- S H N S 6 $3 In a like manner the compound herein referred to as 2-hydroxypyridine-1-oxide, although generally represented as:

I -OH 3,787,417 Patented Jan. 22, 1974 is believed to be a mixture of two tautomeric isomers as shown below: I

This tautomerism will not be alluded to hereinafter, it being understood that the tautomeric forms of I and H are included when referring to the compounds of this invention either by formulae such as I and H or by name. The compounds of this invention can be prepared by a method which comprises interacting 2-marcaptopyridinel-oxide or 2-hydroxypyridine-l-oxide, preferably in. the form of a soluble salt, such as an alkali metal salt or ammonium salt thereof, with a dialkyltin salt of a lower molecular weight organic or inorganic acid in a solvent for the reactants and recovering the reaction product.

Dialkyltin salts suitable for use as starting materials of the process of this invention have the formula:

wherein R and R" are independently selected from the group consisting of alkyl of from 4 to 8 carbon atoms and X is the anion of a lower molecular weight inorganic or organic acid. The anions which may be mentioned include nitrates, acetates, formates, sulfates and halides. Suitable anions have an atomic or molecular weight below about 127.

Preferably, the reaction is carried out using substantially stoichiometric proportions of the two reactants. The reaction can be conducted in a wide variety of inert organic solvents. Monohydric alcohols, such as methanol, ethanol, butanol, etc. and hydrocarbon solvents such as benzene, toluene or xylene, are particularly useful solvents. The product can be recovered from the reaction mixture by any of a number of methods well known in the art, such as by filtration to remove insoluble products formed during the reaction following which the desired product can be recovered from the filtrate by evaporation, extraction with solvents or by any other convenient methods.

Useful dialkyltin salts include, for example:

di-n-butyltin dichloride, sec.-butyl n-octyl dichloride, isoamyl n-hexyltin dibromide, di-n-octyltiu dichloride, di-n-octyltin dibromide, di-n-octyltin sulfate, di-n-octyltin dinitrate, di-n-octyltin diacetate, di-isooctyltin diformate, di-isooctyltin diiodide and di-n-heptyl dichloride.

The following examples are illustrative of, but not limitative of, the invention.

EXAMPLE I Di-n-butyltin salt of 2-mercaptopyridine-1-oxide Di-n-butyl tin dichloride was dissolved in 50 ml. of methanol. A solution of 0.10 mole of the sodium salt of Z-mercaptopyridine-l-oxide in 150 m1. of methanol was added to the di-n-butyltin dichloride solution with stirring. Then the mixture was heated on steam bath for 0.5 hour and filtered hot. The filtrate was chilled to 10 C. and 0.035 mole of white crystals, M.P. 9'2 C., was recovered representing a 70 percent yield of the di-nbutyltin salt of Z-mercaptopyridine-l-oxide having the formula:

Analysis.Calcd. for C H N O S Sn (percent): C,

44.4; H, 5.34; N, 5.76; Sn, 24.3. Found (percent): C, 44.35, 44.32; H, 5.36, 5.45; N, 5.80, 5.91; Sn, 22.7.

EXAMPLE II Di-n-octyltin salt of 2-mercaptopyridine1-oxide Il-C 4119 III- 5 1? Sn S N 8 17 i EXAMPLE III Di-n-butyltin salt of 2-hydroxypyridine-l-oxide 0.2 mole of Z-hydroxypyridine-l-oxide was dissolved in methanol. Then 0.2 mole of sodium hydroxide was added to form the sodium salt. To the slurry of the sodium salt of 2-hydroxypyridine-l-oxide was added 0.1 mole of din-butyltin chloride. The reaction mass was stirred for 30 minutes and then was filtered. The filtrate was concentrated on a steam bath to a volume of 150 ml. and on cooling 0.091 (91 percent of the theoretical yield) mole of the di-n-butyltin salt of Z-hydroxypyridine-l-oxide having the formula:

EXAMPLE IV Di-n-octyltin salt of Z-hydroxypyridine-l-oxide To di-n-octyltin dichloride, 20 g. (0.05 mole) dissolved in 150 ml. of methanol, there was added 22 g. (0.10 mole) of 2-hydroxypyridine-1-oxide with stirring. Then 6.5 g. of sodium hydroxide dissolved in 100 ml. of methanol was added following which the reaction mixture W38 boiled for 20 minutes and filtered hot. After the filtrate had been concentrated on a steam bath to 115 ml. it was chilled to a temperature of about C. The white solid which precipitated was recovered and then recrystallized from methanol. A total of 12.0 g. of the di-n-octyltin salt of Z-hydroxypyridine-l-oxide, M.P. 68-70 C., (41 percent yield of the theoretical yield) having the formula:

was obtained.

n-CaHrv n-CsH 1 was obtained.

Analysis-Galen]. for C H N O Sn (percent): C, 51.2; H, 7.45; N, 4.97; Sn, 20.9. Found (percent): C, 55.04, 55.29; H, 7.46, 7.54; N, 5.61, 570; Sn, 20.0.

The compounds of this invention are active bactericides and fungicides as indicated y the following in vitro spec- 4 tra tabulated in Tables I and II which follow (data on hexachlorophene being included for comparison).

A=Dt-n-hutyltin salt of Z-mercaptopyridine-l-oxide. B =Di-n-octylt7iu salt of Z-mercaptopyridine-l-ordde. jg =Di-n-octyltiu salt of 2-hydroxypyn'diue-1-oxide.

=Hexael l0rophene.

TABLE II Ant-ifungal spectrum M.I.C., g./ml.

Organism A B C D Candida albicans 8. 5 100. 0 12. 5 Penicillium notatum 0.14 0.63 50. Trichophyton mentcgro yte 0.39 0.28 50.0 Asperigillusfumigatus 0.3 0.63 50.0 Asperigillus m'oer 0.25 1.8 100.0 6.8 Pullutaria pull'ullans 0. 08 0. 72 100. 0

Names of the individual compounds are given in footnotes of Table I.

Although the zinc salt of Z-mercaptopyridine-l-oxide is a highly effective antibacterial agent for many applications, its extremely low solubility in materials, such as organic solvents, prevents its use in certain important applications. In contrast, the compounds of this invention which have appreciable solubility in, for example, methyl alcohol, ethyl alcohol, acetone, hexane, xylene, can be conveniently introduced into a product or process as a solution of the compound in the solvent. In Table Ill which follows the solubility of some of the compounds of this invention in various solvents is shown (data on the zinc salt of 2-mercaptopyridine-l-oxide being included for comparison):

TABLE III Solubility, g./100 ml. at 25 C.

Ethyl Product alcohol Hexane Xylene Zine salt of 2-rnercapt0pyridineloxide Insoluble Insoluble Insoluble Di-n-butyltin salt of 2-mercaptopyridine-l-oxide of Example I 4. 0 0. 1-0. 3 25 Di-n-octyltin salt of 2-mercaptopyridine-l-oxide of Example II 80. 0 74 oxide (Product of Example I) 1000 Triphenyltin salt of 2-mercaptopyridine-loxide Tri-n-butyltin salt of 2-mercaptopyridine-loxide Di-n-octyltin salt of 2-mercaptopyridine-loxide (Product of Example II) 2000 Di-n-octyltin salt of Z-hydroxypyridine-loxide (Product of Example IV) 2000 Since the compounds of this invention possess broad antibacterial and antifungal properties, they are utilized as preservatives in a wide variety of products, as mildew proofing agents, and for sterilization and disinfecting purposes. The compounds of this invention are especially useful as preservatives in leather, paint, paper, etc. and in plastics and other fabrics to render them proof against mildew or other fungus attack. In the protection of fabrics, for example, with a compound of this invention, the compound may be applied or incorporated in the fabric in a number of ways such as by soaking or spray ing it with hexane solution of the compound, for example, ethyl alcohol, hexane, or xylene and then allowing the solvent to evaporate. Suitably an effective amount of a compound of the invention is applied to the substrate, for example, from about 0.001 to 1 percent by weight.

What is claimed is: 1. A compound of the formula:

wherein R and R" are independently selected from the group consisting of alkyl of from 4 to 8 carbon atoms and Ch is a chalcogen selected from the group consisting of sulfur and oxygen.

2. The compound of claim 1 wherein R and R" are each n-butyl and Ch is S.

3. The compound of claim 1 wherein R and R" are each n-octyl and Ch is S.

4. The compound of claim 1 wherein R and R" are each n-butyl and Ch is O.

5. The compound of claim 1 wherein R and R" are each n-octyl and Ch is O.

6. The compound of claim 1 wherein R and R" are the same.

7. The compound of claim 6 wherein Ch is S.

8. The compound of claim 6 wherein Ch is 0.

References Cited UNITED STATES PATENTS 2,867,566 1/ 1959 Weinberg .3......... 260-270 R 3,236,733 2/ 1966 Karsten 260-270 R 3,269,904 8/ 1966 Bernstein 260-270 R 3,284,296 11/ 1966 Freiberg 260-270 R 3,321,480 5/ 1967 Schroder et a1. 260-270 R 3,321,481 5/ 1967 Schroder et al. 260-270 R 3,705,943 12/1972 Kaufman 260-270 R 3,498,985 3/ 1970 Kaufman 260-270 R 3,583,999 6/1971 Damico 260-270 R 3,629,264 12/ 1971 Pardee 260-270 R 3,661,911 5/1972 Meyer 260-270 R OTHER REFERENCES Ismail: Chem. Abstr., vol. 68, col. 13128t, abstracting France 1,475,896, April 1967.

Petridis et al.: Chem. Abstr., vol. 73, col. 30445y (1970).

Manulkin: .lour. Gen. Chem. U.S.S.R., vol. 20, 2076 (1950).

DONALD G. DAUS, Primary Examiner 

